NEUROFIBROMATOSIS TYPE 2

Abstract

Neurofibromatosis type 2 (NF2) is a rare neurocutaneous disorder characterised by bilateral vestibular schwannomas associated with meningiomas, ependymomas and other cranial nerve and peripheral schwannomas. The clinical manifestations of NF2 show varying degrees of severity and age-related differences. Childhood presentation of NF2 also predicts a severe disease course. NF2 is genetically caused by germline mutations of the NF2 gene located on 22q12.17. The NF2 gene encodes a protein called merlin. Merlin associates with several transmembrane receptors and intracellular proteins serving as a tumorsuppressor. The diagnosis of NF2 is established based on clinical criteria, or combined molecular and clinical criteria. Specific genotype and phenotype correlations have been identified so far. Although significant progress in neurosurgery, radio-surgery and auditory rehabilitation have increased the treatment options for individuals with NF2, these show higher mortality rates than in the general population. Thus, tumour surveillance remains the cornerstone of NF2 patient management. Recent advances in the elucidation of the role of merlin have led to the development of biological targeted therapies.